Bisphosphonates, such as alendronate and risedronate, are used for the treatment and prevention of various diseases of bone metabolism. These analytes are very polar and multiply charged. Many other compounds of pharmaceutical or toxicological interest are also charged; such compounds are not well retained on most reversed-phased high pressure liquid chromatography (HPLC) columns, which makes analysis and purification difficult.
Currently, published chromatographic methods for the purification of bisphosphonates include ion pairing methods, derivatization, and ion exchange, with pre- or post-column treatments. Each of these methods has associated disadvantages, such as the incompatibility of certain solvents with mass spectrometric detection, use of harsh or potentially expensive reagents or the need for additional time-consuming work-up steps. Reported detection methods include conductivity, ultra-violet/visible detection, and fluorescence detection.